Contents -- Foreword -- "Et causae quoque aestimatio saepe morbum solvit"* [Celsus: Prooemium 69, De Medicina] -- Preface -- Chapter 1 Challenges Facing the Pharmaceutical Industry in the 21st Century -- Introduction -- The Impact of Cardiac Toxicity on the Pharmaceutical Industry -- References -- Chapter 2 The Cellular Basis of Cardiac Electrophysiology -- Introduction -- The Initiation of the Heart Beat -- The Ventricular Cardiac Action Potential -- The Relationship Between the Cardiac Action Potential and the Electrocardiogram -- Ion Channels Underlying the Cardiac Action Potential -- Sodium channels -- Calcium channels -- Potassium channels -- Cardiac potassium channels -- The transient outward potassium channel -- Delayed rectifier potassium channels -- The ultra rapid delayed rectifier potassium channel -- The HERG potassium channel -- The slowly activating delayed rectifier potassium channel -- Inwardly rectifying potassium channels -- Species-dependent variability of potassium channels -- Potassium channel subunits -- Summary -- References -- Chapter 3 Clinical Arrhythmia Syndromes -- Introduction -- The Long QT Syndrome -- Congenital Long QT Syndrome -- Drug-Induced QT Prolongation -- Summary -- References -- Chapter 4 The Mechanisms Underlying Cardiac Arrhythmias -- Introduction -- Mechanisms Underlying Cardiac Arrhythmias -- Abnormal Automaticity -- Early and Delayed Afterdepolarizations -- Re-entry -- Transmural Dispersion of Repolarization -- How does Action Potential and QT Prolongation Generate Arrhythmias? -- Does the M-Cell Play a Role in Arrhythmia Induction in Humans? -- Using Mouse Models to Study Arrhythmia Mechanisms -- Experimental Studies Exploring the Relationship Between Changes in Transmural Repolarization Gradients and Arrhythmias in Mouse Hearts.

Arrhythmia Mechanisms and Novel Antiarrhythmic Approaches Identified Using the Hypokalemic Mouse Model -- Summary -- References -- Chapter 5 The Mechanisms Underlying Drug-Induced Arrhythmias -- Introduction -- The Classical Model of Drug-Induced QT Prolongation and Proarrhythmia: HERG Blockade -- Additional Mechanisms Contributing to Drug-Induced Arrhythmias -- Drug-Induction Activation of Depolarizing Ion Channels -- Drug-Induced Changes in Ion Channel Expression -- Drug-Induced Sodium Channel Dysfunction -- Summary -- References -- Chapter 6 Assessing Cardiac Safety in Drug Development -- Introduction -- Preclinical Evaluation of Cardiac Drug Safety -- The ICH S7B Guidelines -- Single Cell Safety Studies -- The Purkinje Fiber Model -- The Ventricular Wedge Model -- Isolated Heart Models -- In Vivo Models -- The Impact of Species-Related Differences in Cardiac Electrophysiology on Preclinical Drug Safety Assessment -- Methods to Provoke Arrhythmias in Preclinical Studies -- Programmed electrical stimulation -- Reductions in the extracellular K+ concentration -- Clinical Evaluation of Cardiac Safety -- The Thorough QT study -- Thorough QT study design -- Additional Biomarkers to Detect Drug-Induced Proarrhythmia -- Variability of repolarization -- Changes in the morphology of the T wave -- Measurements of Tpeak - Tend -- Recent Case Studies of Drug-Induced Proarrhythmia -- Propoxyphene-Induced Cardiac Toxicity -- Clinical and Experimental Studies of Propoxyphene-Induced Cardiac Toxicity -- Regulatory Assessment of Propoxyphene's Cardiac Safety Profile -- Dolasetron-Induced Cardiac Toxicity -- Clinical and Experimental Studies of Dolasetron-Induced Cardiac Toxicity -- Regulatory Assessment of Dolasetron's Cardiac Safety Profile -- Summary -- References -- Chapter 7 Pediatric Cardiac Safety -- Introduction.

Cisapride-Induced Pediatric Cardiac Toxicity -- Potential Mechanisms Underlying Cisapride-Induced Cardiac Toxicity in Pediatric Patients -- The proarrhythmic effects of drugs in the developing heart -- Drug-Induced Cardiac Toxicity in the Embryonic Heart -- Summary -- References -- Chapter 8 Drug-Induced Atrial Fibrillation -- Introduction -- Atrial Fibrillation -- Bisphosphonate-Induced Atrial Fibrillation -- Adenosine-Induced Atrial Fibrillation -- Corticosteroid-Induced Atrial Fibrillation -- Implications for Cardiac Safety Testing During Drug Development -- Summary -- References -- Chapter 9 Navigating the Future Path of Cardiac Drug Safety -- Introduction -- Disease-Driven Approaches to Cardiac Safety -- Emerging Technologies for Cardiac Safety Assessment -- Zebrafish -- Stem Cells -- New Proarrhythmic Paradigms -- Engagement of Key Stakeholders to Advance Cardiac Safety Assessments -- References -- Index.